Size-Based HDL Particles and Cardiovascular Risk

High-density lipoprotein cholesterol concentration (HDL-C) is a primary lipid marker used in the ACC/AHA ASCVD pooled cohort equation. However, contemporary studies have demonstrated inconsistencies in the association between HDL-C and cardiovascular risk. Further, therapies that increase HDL-C have failed to improve outcomes. Thus, there is need for a more reliable HDL biomarker.

Measuring total numbers of HDL particles (HDL-P), as compared with HDL-C, has yielded a more consistent association with myocardial infarction (MI). While some studies have suggested that the size of HDL particles can predict ASCVD, these findings have been inconsistent, and the studies have been limited by small numbers and crude distinction of HDL sizes. What we still do not know is whether specific size-based HDL particles confer additional prognostic information to traditional ASCVD risk markers.

At #AHA22, we had the honor of sharing the results of a study in which we assessed the association between seven more refined and precise sized-based HDL particles with incident MI and ischemic stroke. We tested this hypothesis in a large, pooled cohort of more than 15,000 participants across four cohorts and two countries. Adjusting for traditional risk factors, including HDL-C, higher levels of two of the seven HDL size-based particles (smallest particle and a medium-sized particle) were linked to lower MI risk. Intriguingly, none of the large HDL size-based particles were linked to reduced MI risk. Overall, the size-based HDL particles improved the ability to predict the risk of MI beyond traditional risk factors, though the magnitude of improvement was modest. No size-based particles were linked to stroke when adjusted for HDL-C.

We also studied the impact of Black race on the association between size-based HDL particles and ASCVD risk. In prior studies, we had shown that neither HDL-C nor total HDL particles predicted MI risk in Black individuals. In the current study, we found in Black participants that higher levels of the smallest HDL particles were linked to lower MI risk whereas medium-sized HDL particles were no longer associated with MI. These findings are novel and suggest that more precise size-based HDL markers may provide ASCVD risk information overall and, specifically, in Black individuals. Future studies are needed to test the clinical utility of measuring size-based HDL particles.